Because of the recent striking increase in the incidence of clear- cell adenocarcinoea of the lower genital tract in young females as a result of prenatal exposure to diethylstilbestrol (DES), the Registry of Clear-cell Adenocarcinoma of the Genital Tract in Young Females has been established to investigate in depth the epidemiology, clinico-pathologic features, and therapy of these tumors. All cases of clear-cell adenocarcinoma of the genital tract in females born after 1940 are being investigated in detail whether or not there is a history of maternal medication. In addition all vaginal malignancies occurring in young females associated with maternal hormonal therapy are being studied. Cases are currently entered in the Registry from throughout the world. Through yearly follow-up of all accessioned cases, detailed evaluation of sites and therapy of tumor recurrences as well as cause of death, autopsy data, etc. are recorded. These studies should establish the natural history of the disease, its optimal therapy, and the role of hormones other than DES in the pathogenesis of these cancers. The precancerous potential of vaginal adenosis is being studied including its optimal management, as well as the possible use of local progesterone as a method of therapy.